Chapter 31 - BCS1L Mutations as a Cause of Björnstad Syndrome–GRACILE Syndrome Complex III Deficiency

Abstract

The cases of two children with pathogenic mutations in BCS1L with clinical features of both Björnstad syndrome (congenital deafness and pili corti) and GRACILE syndrome (intrauterine Growth Retardation, Aminoaciduria, Cholestasis, Iron overload, Lactic acidosis, and Early death) are reported. The initial cases of Björnstad syndrome were reported as cases having normal language and cognitive function, while children with GRACILE syndrome have severe-to-profound cognitive delays. All reported phenotypes caused by mutations in BCS1L follow an autosomal recessive pattern of inheritance, with the carrier parents having no sign of illness and illness in the case caused by pathogenic mutations inherited in trans. Children with mutations in BCS1L may present with a wide spectrum of mitochondrial phenotypic features, and this variability is a result of the variable pathogenicity of the mutations. It also appears that mutations themselves may be specific for Björnstad syndrome or for GRACILE, and that some of the mutations associated with Björnstad syndrome have a milder phenotype. Cases carrying one of each type of mutation appear to have a mixed phenotype. Recognizing the specific phenotypes will result in an earlier diagnosis and lead the clinician to the use of limited biochemical screening tests and genetic testing confirmation for mutations in the BCS1L gene. Treatment is supportive, as there is no known cure for these disorders.